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Promises and challenges of genomic newborn screening (NBS) – lessons from public health NBS programs

Pediatric Research volume 97, pages 1327–1336 (2025)Cite this article

Abstract

Newborn screening (NBS) in the United States began in the 1960s to detect inborn errors of metabolism that benefited from presymptomatic treatment compared with treatment after the development of symptoms and diagnosis. Over time, it expanded to include endocrinological disorders, hematological disorders, immunodeficiencies, and other treatable diseases such as lysosomal storage diseases (LSD), cystic fibrosis, X-linked adrenoleukodystrophy, and spinal muscular dystrophy. This expansion has been driven by new technologies (e.g., tandem mass spectrometry) and novel treatments (e.g., enzyme replacement therapy and stem cell transplant for LSDs). Advances in next-generation gene sequencing (NGS) enable rapid identification of many additional conditions that might benefit from early presymptomatic intervention. We review the NGS technologies that evolved as diagnostic testing and suggest issues to be resolved before their potential application to screening the asymptomatic population. We illustrate the importance of selecting diseases to be screened and propose recommendations to follow when variants of uncertain significance are found. We address ethical issues around achieving equity in the sensitivity of genomic NBS, access to follow-up and management, especially for people from diverse backgrounds, and other considerations. Finally, we discuss the potential benefits and harms of genomic NBS to the overall health of children with monogenic diseases.

Impact

  • Genomic newborn screening programs are ongoing worldwide.

  • Public discussion is needed as to whether genomic newborn screening should be offered as a public health program and, if so, what conditions should be screened for.

  • Providers should understand that the sensitivity of genomic newborn screening is especially low for newborns from non-European populations.

  • Methylation, large structural variants and repeat expansion variants are not amenable to next-generation sequencing-based genomic newborn screening.

  • The article serves as a comprehensive guide to understanding issues that need to be solved before genomic newborn screening is implemented as a public health program.

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Data availability

Data sharing is not applicable as no raw data was generated as part of this review.

Notes

  1. Nussbaum, McInnes, and Willard, Thompson & Thompson Genetics in Medicine E-Book.

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Author information

Authors and Affiliations

  1. The Ohio State University College of Medicine Department of Pediatrics, Columbus, OH, USA

    Mari Mori, Bimal P. Chaudhari, Margie A. Ream & Alex R. Kemper

  2. Division of Genetic and Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

    Mari Mori & Bimal P. Chaudhari

  3. Division of Neonatology, Nationwide Children’s Hospital, Columbus, OH, USA

    Bimal P. Chaudhari

  4. The Steve and Cindy Rasmussen Institute of Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

    Bimal P. Chaudhari

  5. Division of Division of Child Neurology, Nationwide Children’s Hospital, Columbus, OH, USA

    Margie A. Ream

  6. Division of Primary Care Pediatrics, Nationwide Children’s Hospital, Columbus, OH, USA

    Alex R. Kemper

Authors
  1. Mari Mori
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  2. Bimal P. Chaudhari
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  3. Margie A. Ream
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  4. Alex R. Kemper
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All authors substantially contributed to the conception of the review, and involved in drafting revising and final approval of the published manuscript.

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Correspondence to Mari Mori.

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Mori, M., Chaudhari, B.P., Ream, M.A. et al. Promises and challenges of genomic newborn screening (NBS) – lessons from public health NBS programs. Pediatr Res 97, 1327–1336 (2025). https://doi.org/10.1038/s41390-024-03689-0

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